石榴汁（PGJ）在多发性骨髓瘤（MM）中的抗增殖和抗血管生成作用。
Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).
作者信息
Tibullo Daniele, Caporarello Nunzia, Giallongo Cesarina, Anfuso Carmelina Daniela, Genovese Claudia, Arlotta Carmen, Puglisi Fabrizio, Parrinello Nunziatina L, Bramanti Vincenzo, Romano Alessandra, Lupo Gabriella, Toscano Valeria, Avola Roberto, Brundo Maria Violetta, Di Raimondo Francesco, Raccuia Salvatore Antonio
机构信息
Section of Hematology, Department of Surgery and Medical Specialties, University of Catania, Catania 95125, Italy.
Department of Biological, Geological and Environmental Sciences, University of Catania, Catania 95125, Italy.
出版信息
Nutrients. 2016 Oct 1;8(10):611. doi: 10.3390/nu8100611.
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.
多发性骨髓瘤（MM）是一种克隆性B细胞恶性肿瘤，其特征是克隆性浆细胞（PC）在骨髓（BM）中积聚，导致骨质破坏和BM功能衰竭。尽管近年来药物治疗取得了进展，但MM在很大程度上仍然是一种无法治愈的疾病。因此，迫切需要新型、有效且毒性较小的药物。在过去几年中，人们对石榴的潜在治疗特性进行了研究，包括癌症的治疗和预防。石榴汁（PGJ）含有多种潜在的活性化合物，包括有机酸、维生素、糖和酚类成分，这些成分都与在肿瘤细胞系中观察到的促凋亡作用有关。本研究的目的是评估PGJ在人多发性骨髓瘤细胞系中的抗增殖和抗血管生成潜力。我们的数据证明了PGJ在MM细胞中的抗增殖潜力；其诱导G0/G1细胞周期阻滞的能力及其抗血管生成作用。有趣的是，硼替佐米/PGJ的序贯联合提高了蛋白酶体抑制剂的细胞毒性作用。我们研究了PGJ对血管生成和细胞迁移/侵袭的影响。有趣的是，我们观察到对管形成、微血管生长主动脉环有抑制作用，并且分别通过伤口愈合和transwell试验显示细胞迁移和侵袭减少。对内皮细胞中血管生成基因表达的分析证实了石榴的抗血管生成特性。因此，给予PGJ可能是一种很好的工具，以利用其抗增殖和抗血管生成作用来确定MM治疗的新策略。最后，本研究支持了这样的证据，即PGJ可能在MM治疗的未来治疗方法中发挥关键作用，以优化硼替佐米的药理作用，特别是作为治疗后的辅助药物。
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